The structure of macromolecular assemblies is investigated with a new combination of methods involving conventional and scanning transmision electron microscopy, computer alignment of single particles and ultivariate statistical analysis. The method makes possible the identification of small conformational differences or chemical labels and allows homogeneous subpopulations to be extracted from a heterogeneous set of molecule images. The method will be applied to the study of prokaryotic and eukaryotic ribosomal subunits, acetylcholine receptor, glutamine synthetase, and hemocyanine molecules in collaborative projections. The focus of the research will be on the ribosomal structure. Specimen preparation methods will be varied to find contitions to preserve three-dimensional information. Averages of different views, purified and quantitatively characterized by multivariate statistics will be used in the three-dimensional reconstruction of macromolecular assemblies.